High tumor necrosis factor-α/interleukin-10 ratio is associated with hepatocellular carcinoma in patients with chronic hepatitis C

•TNF-α levels were significantly higher in individuals with HCC.•IL-10 levels were significantly higher in HCV patients with mild fibrosis.•High TNF-α/IL-10 ratio was associated with HCC occurrence.•TNF-α/IL-10 ratio may predict severe hepatic disease in HCV infected individuals. Hepatitis C virus (...

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Published in:	Cytokine (Philadelphia, Pa.) Vol. 62; no. 3; pp. 421 - 425
Main Authors:	Aroucha, D.C.B.L., do Carmo, R.F., Moura, P., Silva, J.L.A., Vasconcelos, L.R.S., Cavalcanti, M.S.M., Muniz, M.T.C., Aroucha, M.L., Siqueira, E.R.F., Cahú, G.G.O.M., Pereira, L.M.M.B., Coêlho, M.R.C.D.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-06-2013
Subjects:	blood serum Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - complications Carcinoma, Hepatocellular - genetics cell-mediated immunity chronic hepatitis Cytokine diabetes disease severity Female fibrosis HCC HCV Hepatitis C virus Hepatitis C, Chronic - blood Hepatitis C, Chronic - complications Hepatitis C, Chronic - genetics hepatoma Humans IL-10 immune response inflammation interleukin-10 Interleukin-10 - blood liver Liver Cirrhosis - blood Liver Cirrhosis - genetics Liver Neoplasms - blood Liver Neoplasms - complications Liver Neoplasms - genetics Male Middle Aged Multivariate Analysis necrosis patients polypeptides regression analysis risk Risk Factors TNF-α Tumor Necrosis Factor-alpha - blood HCC HCV TNF-α IL-10 Cytokine
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Summary:	•TNF-α levels were significantly higher in individuals with HCC.•IL-10 levels were significantly higher in HCV patients with mild fibrosis.•High TNF-α/IL-10 ratio was associated with HCC occurrence.•TNF-α/IL-10 ratio may predict severe hepatic disease in HCV infected individuals. Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk for the development of HCC increases with the severity of liver inflammation and fibrosis. The hepatic inflammation caused by HCV involves host regulatory immune response, which is mediated by cytokines with anti-viral role upon the interaction of viral polypeptides with innate and adaptive immunity. Two cytokines; tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) play key roles in the regulation of cellular immune response in HCV infection. The aim of the present study was to determine the levels of IL-10 and TNF-α, as well as the ratio of TNF-α and IL-10 serum levels in patients with HCV and HCC caused by HCV (HCC–HCV). The study included 173 patients with chronic HCV. TNF-α and IL-10 serum levels were measured by ELISA (R&D Systems, Inc.). In the present study, 54 patients presented liver mild fibrosis, 68 had severe fibrosis and 51 patients had HCC. After adjustment in the multivariate regression analysis, the following variables remained significantly associated with HCC–HCV occurrence: diabetes (p=0.012 OR 10.44 CI 1.66–65.60), IL-10 lower levels (p<0.0001 OR 0.83 CI 0.78–0.89) and TNF-α higher levels (p<0.0001 OR 1.19 CI 1.11–1.28). Individuals with HCC presented higher TNF-α/IL-10 ratio than those with fibrosis grade F4, F3 or F0+F1+F2 (p=0.0003, p<0.0001, p<0.0001, respectively). Patients with HCC were associated to higher index TNF-α/IL-10 ratio, suggesting that the unbalanced production of these cytokines may represent progression to the liver disease severity in HCV infected patients.
Bibliography:	http://dx.doi.org/10.1016/j.cyto.2013.03.024 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1043-4666 1096-0023
DOI:	10.1016/j.cyto.2013.03.024